#Rheumatology Fun

Let’s take a deep dive into a unique subset of rheumatic diseases

This week's RTL guest tweetorial from @MithuRheum!

CASE 1:

A 52 yo male presents to clinic w/ 6 months of hand ulcerations on the dorsal surface of the hands & elbow, oral ulcers, a violaceous periorbital rash and mild arthralgias

CT chest demonstrates nodular opacities

Based on the clinical presentation and photograph of the ulcers, which of the following is the most likely diagnosis?

On exam:

You note bilateral inspiratory crackles at the bases, although he's breathing comfortably on room air

Musculoskeletal exam reveals no synovitis

Manual muscle strength exam is 5/5 throughout all major muscle groups

Which laboratory test do you order next?

Inflammatory myopathies:

Aka idiopathic inflammatory myopathies (IIM); can present with a variety of symptoms & most commonly *symmetric proximal muscle weakness*

Other signs include: heliotrope rash , Gottron’s papules (see image), interstitial lung disease, dysphagia

IIM mechanism?

Lymphocytic infiltrates in muscle tissue and expression of autoantibodies against muscle are part of the immune mechanisms contributing to myositis!

T- and B-cell proliferation and activation can be seen on muscle biopsy

After a comprehensive physical exam, here is some of the diagnostic workup that should be considered if you have a patient and are concerned for myositis:

Laboratory workup reveals:
+ANA 1:160 (homogenous)
Normal CK & aldolase

You suspect this patient has MDA-5 Dermatomyositis (DM), an idiopathic inflammatory myopathy (aka myositis)

MDA-5 DM can be clinically amyopathic w/ rapidly progressive interstitial lung disease (ILD)

Clinical features in MDA-5 DM include:
Cutaneous ulcers
Oral ulcers
Alopecia
Pulmonary symptoms 2/2 ILD

MDA-5 myositis can be clinically amyopathic!

this means that pts may *not* have muscle weakness on exam & can have normal muscle enzymes (CK, AST, ALT, aldolase)

- skin biopsy now shows interface dermatitis

because of *new* dyspnea on exertion , you evaluate the patient and admit for further workup

Which laboratory marker should be checked to determine prognosis?

Ferritin level is an important prognostic marker for development of rapidly progressive ILD (RP-ILD) & mortality

From a 2012 study:

MDA-5 DM patients with RP-ILD had ferritin than those without ILD

MDA-5 DM patients who died also had ferritin than patients who lived

Notably, there was *no* difference in CRP levels between these two MDA-5 DM groups: w/ RP-ILD & w/o RP-ILD

it's possible the hyperferritinemia is not simply a reflection of the acute phase response, but a true pathophysiological mechanism

a viral trigger may be associated!

What is MDA-5?

MDA5 is an interferon-induced RNA helicase which senses ssRNA viruses (e.g. SARS-CoV-2!)

Some hypothesize MDA-5 DM as a form of macrophage activation syndrome - given high ferritin & IL-18 levels - that targets skin and lungs related to an infectious trigger

CASE 2:

Suppose instead you have a patient with:

Psoriatic-like lesions
Hyperkeratotic papules on palmar & digital flexor surfaces
This lesion on the roof of the mouth

Which myositis-specific antibody do you suspect will come back positive on the myositis antibody panel in this patient?

... this patient has TIF1y dermatomyositis

TIF1y DM can cause psoriasis-like lesions & this finding of an ovoid palatal patch (symmetric curved erythema on hard palate w/ white macules)

It's important to screen patients w/ DM for malignancy, especially if TIF1y positive!

So... why do these antibodies matter, clinically?

recognizing specific phenotypes associated with myositis-specific antibodies (MSAs) can help identify the particular IIM subtype and its various systemic manifestations

More examples?

see

Here's a reference chart to keep the different types of myositis-specific antibodies (MSAs) organized!

Keep in mind that some autoantibodies are *non-specific*

While they can be detected in patients with myositis, they are also seen in other autoimmune disorders (e.g. Ro52 in scleroderma)!

these are called myositis-associated antibodies (MAAs)

MSAs vs MAAs:

One can check the myositis antibody panel to see which of the MSAs are included at their institution

Of note: specific types of inflammatory myopathies – such as HMGCR necrotizing myopathy – are *not* included in the MyoMarker 3 panel (most commonly used myositis Ab panel)

To learn more about the identification of myositis-specific antibodies (MSAs) and association with distinct clinical phenotypes, check out this article by myself and @LisaCriscione:

https://www.the-rheumatologist.org/article/myositis-specific-antibodies-identified/

REFs (1/2):

(1) https://pubmed.ncbi.nlm.nih.gov/31365803/ 
(2) Gono et. al. Rheumatology (Oxford). 2012 Sep;51(9):1563-70.
(3) Gono et. al. Rheumatology (Oxford). 2010 Jul;49(7):1354-60.
(4) Fiorentino et. al. J Am Acad Dermatol. 2011 Jul;65(1):25-34.

REFs (2/2):

(5) Moghadam-Kia S et al. Curr Rheumatol Rep. 2018 Oct 31;20(12):78.
(6) Bernet et. al. JAMA Dermatol. 2016 Sep 1;152(9):1049-51.
(7) Wolstencroft PW & Fiorentino DF. Curr Rheumatol Rep. 2018 Apr 10;20(5):28.
(8) https://www.sciencedirect.com/science/article/pii/S0966842X18301793

@DavidLeverenz @LisaCriscione @TheMyositisAssc @MyositisSupport @UKMyositis @didemsayginmd @docrota @drhectorchinoy @pekor002 @DrJohanLim @k_vaishnani @AnnKumfer @medrants